This invention relates generally to a formulation for treating a patient susceptible to or suffering from a cardiovascular disorder or disease, and more particularly, but not by way of limitation, to a formulation for preventing and treating atherosclerosis, arteriosclerosis, congestive heart failure, arterial stenosis, re-stenosis, smooth muscle cell. hypertrophy, cardiac cell hypertrophy, thrombogenicity, clotting disorders, platelet disorders, myocardial infarction, cerebrovascular ischemia, peripheral vascular ischemia, angina pectoris or hypertension.
Cardiovascular disorders and diseases, and their associated complications are a principal cause of disabilities and deaths of individuals in the United States and Western Europe. For example, in recent years more than 500,000 deaths have occurred annually in the United States alone as a result of coronary artery disease, and an additional 700,000 patients have been hospitalized for myocardial infarction.
There has been an ongoing search for effective long term treatment for disorders and diseases of the heart and arteries, such as atherosclerosis, arteriosclerosis, congestive heart failure, angina pectoris, and other disorders and diseases associated with the cardiovascular system. Prior treatments for such disorders or diseases include administration of vasodilators, angioplasty and by-pass surgery, for example. Such treatments have met with great disapproval due to risks versus benefits gained by the various treatments. Such treatments have serious shortcomings in long-term effectiveness. The use of vasodilator drugs and mechanical treatments for acute and chronic occlusive vascular diseases of the heart, central and peripheral vascular systems have to date been ineffective for favorable long-term results. The outcome with current treatments is minimally impacted because the treatments are directed toward effects of the underlying disease process rather than initial molecular cause of the disease or disorder.
For example, the rationale for vasoactive drugs is to reduce blood pressure by acting directly or indirectly on vascular and/or cardiac smooth muscle, thereby decreasing vascular resistance to flow. Such drugs do not treat initial cause of elevated pressure and abnormal flow. Rather, they seek to reduce the resulting effect of the disease or disorder. Such drugs activate the sympathetic nervous system by way of a baroreceptor reflex to produce an increased heart rate and force of myocardial contraction which are not beneficial effects. Other side effects from such drugs include headache, heart palpitations, anxiety, mild depression, dry-mouth, unpleasant taste in the mouth, nausea, vomiting, angina, myocardial infarction, congestive heart failure, decreased cardiac output, fluid retention, fatigue, and weakness. Pharmacological treatment is not specific in its effect on the initial molecular cause of the disease activity, and treats a limited spectrum of effects in the diseases which are multifactorial.
As a further example, improved outcome in atherosclerotic vascular diseases is seen with cholesterol reduction and drug treatment for lipid disorders. These treatments do not prevent cellular or molecular reactions attributed to platelets, macrophages, neutrophils, lymphocytes, smooth muscle cells, and other cell types known to be involved in atherosclerosis and complications of the disease.
Likewise, thrombolytic therapy, angioplasty and bypass surgery have been minimally successful long-term. Current mechanical and pharmacological treatments focus on a partial or completely occluded vessel where, at the particular site, it is either unclogged or bypassed with connecting vessels. These treatments fail to address physiologic derangements of homeostatic systems which allow the occlusive process to begin and progress. Accordingly, there is frequent recurrent occlusion in the initially treated vessel, as well as microembolism from incomplete resolution of thrombus at the occlusive site treated; and no treatment for sites not judged to be adequately occluded or stenotic.
There remains a great need for treatment which prevents failure of homeostatic controls and which restores these controls once derangements begin to develop. Restoration of endogenous regulatory systems and cellular domains to a healthy state prevents stenosis, occlusion, thrombosis, and thromboembolic processes which occur as a consequence of such derangements. Continuous and episodic restoration of control in molecular processes which finely regulate homeostasis, prevent atherosclerosis, variants thereof, hypertension, congestive heart failure, macro and micro-thrombosis and thromboembolism, myocardial infarction, cerebrovascular accident, and complications of these disease processes.
It is a conception of the inventor that a cellular matrix composed of heparin-arginine-water polymers is responsible for controlling molecular milieu comprising the human cellular environment. It is these polymers which determine the protein distribution, functionality, DNA-RNA transcription regulation, and the physical properties of cells.
It is an object of the present invention to provide a composition of material comprised of exogenous heparin and arginine or functional analogs or physiologically acceptable salts thereof, which is directed to preventing and minimizing dysfunctional atomic and molecular interactions within human cellular environments and membranes, such interactions being associated with cardiovascular disease or disorders, by co-administration of said composition, in which components of the endothelium are stimulated to therapeutically modulate adverse molecular reactions associated with cardiovascular disease or dysfunction.
It is another object of the present invention to provide a composition of material which is directed to retarding adverse consequences of free radicals generated in human cellular domains relating to cardiovascular disease or disorders, by co-administration of exogenous heparin and arginine or functional analogs or physiologically acceptable salts thereof.
It is still a further object of the present invention to trigger an endogenous heparin production cycle within human cellular environments and membranes by co-administration of exogenous heparin and arginine or functional analogs or physiological acceptable salts thereof.
It is still a further object of the present invention to provide a composition of material which is directed to decreasing thrombogenicity, repairing cellular processes, and improving blood flow properties that are associated with thrombosis and hypoxia within a human cellular environment, by co-administration of exogenous heparin and arginine or functional analogs or physiologically acceptable salts thereof.
It is an object of the present invention to avoid known side effects such as thrombocytopenia and bleeding attendant with the administration of heparin alone, by co-administration of heparin and arginine.
It is a further object of the invention to provide a composition of material comprised of exogenous heparin and arginine or functional analogs or physiologically acceptable salts thereof, in co-administered therapeutic doses for human beings, which is directed to treatment and prevention of cardiovascular disease or disorders.